Scn4a sodium channel, voltage-gated, type IV, alpha [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Scn4aprovided by MGI
Official Full Name: sodium channel, voltage-gated, type IV, alphaprovided by MGI
Primary source: MGI:MGI:98250
See related: Ensembl:ENSMUSG00000001027 AllianceGenome:MGI:98250
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: mH2; SkM1; Nav1.4
Summary: Enables voltage-gated sodium channel activity. Acts upstream of or within sodium ion transport. Predicted to be integral component of plasma membrane. Predicted to be part of voltage-gated sodium channel complex. Predicted to be active in axon. Is expressed in heart; heart ventricle; and testis. Used to study hyperkalemic periodic paralysis and hypokalemic periodic paralysis. Human ortholog(s) of this gene implicated in congenital myasthenic syndrome 16; hyperkalemic periodic paralysis; and paramyotonia congenita of Von Eulenburg. Orthologous to human SCN4A (sodium voltage-gated channel alpha subunit 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in mammary gland adult (RPKM 6.9), heart adult (RPKM 4.1) and 3 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 E1; 11 68.91 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (106208374..106256385, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (106317545..106365559, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Voltage-dependent Ca(2+) release is impaired in hypokalemic periodic paralysis caused by CaV1.1-R528H but not by NaV1.4-R669H.
Title: Voltage-dependent Ca(2+) release is impaired in hypokalemic periodic paralysis caused by Ca(V)1.1-R528H but not by Na(V)1.4-R669H.
we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed 'draggen' mutation) as a novel disease enhancer
Title: A genetic modifier suggests that endurance exercise exacerbates Huntington's disease.
NaV1.4 null mice have latent myasthenia and a right shift of the force-stimulus relation, without evidence of periodic paralysis. Sodium current density was half that of wild-type muscle and no compensation by retained expression of the foetal NaV1.5 isoform was detected. Mice null for NaV1.4 did not survive beyond the second postnatal day.
Title: Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.
In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms
Title: Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis.
HyperKPP phenotype does not depend solely on the NaV1.4 content.
Title: Contractile abnormalities of mouse muscles expressing hyperkalemic periodic paralysis mutant NaV1.4 channels do not correlate with Na+ influx or channel content.
Homozygous R669H mice had a robust hypokalemic periodic paralysis phenotype, with transient loss of muscle excitability and weakness in low-K+ challenge, insensitivity to high-K+ challenge, dominant inheritance, and absence of myotonia.
Title: A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis.
The skeletal muscle isoform of Na(v)1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na(+) concentrations found in muscle from mdx mice.
Title: Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death.
A distinct autosomal recessive myotonic mouse in the C57BL/6 background (line B6MT)is reported in which the Scn4a gene shows polymorphism with no functional consequences.
Title: A novel murine myotonia congenita without molecular defects in the ClC-1 and the SCN4A.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (6) 1 citation
Chemically induced (ENU) (1) 1 citation

General gene information

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Markers

RH94568 (e-PCR)
- UniSTS:119816

SCN4A (e-PCR)
- UniSTS:504597

Scn1a (e-PCR), detects polymorphism
- UniSTS:516634

Scn4a (e-PCR), detects polymorphism
- UniSTS:516642

Scn4a (e-PCR), detects polymorphism
- UniSTS:516643

UniSTS:224857 (e-PCR)
- UniSTS:224857

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables monoatomic cation channel activity	IEA Inferred from Electronic Annotation more info
enables monoatomic ion channel activity	IEA Inferred from Electronic Annotation more info
enables sodium channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated sodium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in choline transport	ISO Inferred from Sequence Orthology more info
involved_in membrane depolarization during action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic cation transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of skeletal muscle contraction by action potential	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of voltage-gated sodium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated sodium channel complex	IC Inferred by Curator more info	PubMed
part_of voltage-gated sodium channel complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: sodium channel protein type 4 subunit alpha

Names: sodium channel alpha-subunit; sodium channel protein skeletal muscle subunit alpha; sodium channel protein type IV subunit alpha; sodium channel, voltage-gated, type IV, alpha polypeptide; voltage-gated sodium channel subunit alpha Nav1.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001403641.1 → NP_001390570.1 sodium channel protein type 4 subunit alpha

Status: VALIDATED

Source sequence(s)

AL604045

UniProtKB/TrEMBL

G3X8T7

Related

ENSMUSP00000021056.8, ENSMUST00000021056.8
NM_133199.3 → NP_573462.2 sodium channel protein type 4 subunit alpha

See identical proteins and their annotated locations for NP_573462.2

Status: VALIDATED

Source sequence(s)

AL604045

Consensus CDS

CCDS48961.1

UniProtKB/Swiss-Prot

A2VDE9, B1ARK0, Q9ER60

UniProtKB/TrEMBL

G3X8T7

Conserved Domains (3) summary

cd13433
Location:1290 → 1342

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1024 → 1298

Ion_trans; Ion transport protein

pfam06512
Location:810 → 1020

Na_trans_assoc; Sodium ion transport-associated